The objective of this UM1 application is to maintain and enhance the core infrastructure of the Breast Cancer Family Registry (BCFR), an international resource of multi-generational families established for interdisciplinary collaborative research on breast cancer. The BCFR Cohort, established in 1995 at 6 sites is comprised of 34,000 individuals from 11,900 families who provided data on family history and epidemiologic risk factors as well as bio specimens. Over the next five years, the BCFR investigator team will continue 1) to actively follow the family cohort using common instruments and protocols, update the cancer family histories to identify new breast and other cancers in the families, and administer a follow-up questionnaire to update baseline epidemiologic data; 2) to maintain the extensive data and bio specimen resources and enhance them by conducting pathology review for all new breast cancers ascertained since baseline, completing molecular sub typing of tumors, and completing genotyping of known common breast cancer susceptibility variants; 3) to collect new data on screening, uptake of risk reductive and preventive health behaviors, knowledge of genetic disease, and uptake of genetic testing and communication to family members that will facilitate the translation of findings into clinical practice; and 4) to continue and expand collaborations with external investigators by sharing of BCFR data and bio specimen resources for a wide range of studies of gene discovery, cancer-related outcomes, risk factors in high-risk individuals, behavioral interventions and cancer prevention trials among at-risk family members. The BCFR Cohort is unique in that it is family-based and the first large prospective study of breast cancer risk for women at a continuum of risk. In addition to the unaffected cohort, the BCFR has one of the largest affected cohorts and will therefore provide a powerful resource for translational and clinical studies of recurrences, second primaries and survival.